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Dopamine receptor 1 on CaMKII-positive neurons within claustrum mediates adolescent cocaine exposure-induced anxiety-like behaviors and electro-acupuncture therapy

 Liying Chen  ;  Zhaoyu Liu  ;  Ziheng Zhao  ;  Demin Du  ;  Weichao Pan  ;  Xiaoyan Wei  ;  Jiaxun Nie  ;  Feifei Ge  ;  Jianhua Ding  ;  Yu Fan  ;  Hee Young Kim  ;  Xiaowei Guan 
 THERANOSTICS, Vol.13(10) : 3149-3164, 2023-05 
Journal Title
Issue Date
Animals ; Anxiety / chemically induced ; Anxiety / therapy ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism ; Claustrum* / metabolism ; Cocaine* / metabolism ; Cocaine* / pharmacology ; Male ; Mice ; Neurons / metabolism ; Receptors, Dopamine D1 / metabolism
Adolescent cocaine exposure ; Anxiety ; Claustrum ; D1RCaMKII ; Electro-acupuncture
Adolescent cocaine exposure (ACE) increases risk of developing psychiatric problems such as anxiety, which may drive relapse in later life, however, its underlying molecular mechanism remains poorly understood.

Methods: ACE male mice model were established by exposing to cocaine during adolescent period. Elevated plus maze (EPM) were used to assess anxiety-like behaviors in mice. Within claustrum, local injection of SCH-23390, a specific antagonist for dopamine receptor 1 (D1R), or D1R knocking-down virus were used to regulate D1R function or expression on CaMKII-positive neurons (D1RCaMKII) in vivo. Electro-acupuncture (EA) treatment was performed at acupoints of Baihui and Yintang during withdrawal period.

Results: We found that ACE mice exhibited anxiety-like behaviors, along with more activated CaMKII-positive neurons and increased D1RCaMKII levels in claustrum during adulthood. Inhibiting D1R function or knocking-down D1RCaMKII levels in claustrum efficiently reduced claustrum activation, and ultimately suppressed anxiety-like behaviors in ACE mice during adulthood. EA treatment alleviated ACE-evoked claustrum activation and anxiety-like behaviors by suppressing claustrum D1RCaMKII.

Conclusion: Our findings identified a novel role of claustrum in ACE-induced anxiety-like behaviors, and put new insight into the D1RCaMKII in the claustrum. The claustrum D1RCaMKII might be a promising pharmacological target, such as EA treatment, to treat drug-induced anxiety-like behaviors.
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1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hee Young(김희영) ORCID logo https://orcid.org/0000-0002-2495-9115
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